aza-Claisen Rearrangement Research Articles

A stereoselective synthesis of (+)-physoperuvine using a tandem aza-Claisen rearrangement and ring closing metathesis reaction

A stereoselective synthesis of (+)-physoperuvine, a tropane alkaloid from Physalis peruviana Linne has been developed using a one-pot tandem aza-Claisen rearrangement and ring closing metathesis reaction to form the key amino-substituted cycloheptene ring.

Doubly diastereoselective [3,3]-sigmatropic aza-Claisen rearrangements

The doubly diastereoselective [3,3]-sigmatropic aza-Claisen rearrangement of silylketene aminals derived from 5-substituted (3S,4E,alphaR)-1-benzyloxy-3-[N-acyl-N-(alpha-methylbenzyl)amino]pent-4-enes furnishes 2,3-disubstituted (R)-N-alpha-methylbenzyl (2S,3R,4E)-7-benzyloxyhept-4-enamides in >90% de under the "matched" control of both stereogenic centres. Rearrangement of the "mismatched" diastereomeric (3R,4E,alphaR)-substrates proceeds with low diastereoselectivity. The substrate scope of the doubly diastereoselective rearrangement of the "matched" substrates in which two new stereogenic centres are created has been delineated.

A Novel Synthetic Approach to C-Glycosyl-D- and L-Alanines

C-Glycosyl-(S)- and (R)-alanines 12a and 12b were synthesized from the known β-C-glycoside 1. The nitrogen function was introduced by aza-Claisen rearrangement of the allylic thiocyanate 7, derived from the corresponding alcohol 6. The absolute configuration of the newly created chiral carbon center (C-3) was assigned by X-ray diffraction analysis of the intermediate 3(S)-isothiocyanato-d-glycero-d-galacto-decose 8a.

Microwave Accelerated Aza-Claisen Rearrangement

A study of microwave-induced and standard thermal Overman rearrangement of selected allylic trichloroacetimidates 1a-1f, 6-8 to the corresponding acetamides 2a-2f, 9- 11 is reported. The microwave-assisted rearrangement of trifluoroacetimidate 13 is also described. Using this methodology, an efficient access to versatile allylic trihaloacetamides building synthons was established.

Sequential Aza-Claisen Rearrangement and Ring-Closing Metathesis as a Route to 1-Benzazepine Derivatives

A synthetic strategy based on sequential application of aza-Claisen rearrangement and ring-closing metathesis reaction as key steps has been developed for the synthesis of various 1-benzazepine derivatives of pharmaceutical relevance.

Enantiopure 2-Substituted Glyceraldehyde Derivatives by Aza-Claisen Rearrangement or C-Alkylation of Enamines

2-Alkyl derivatives of butane-2,3-diacetal (BDA) protected glyceraldehyde were stereoselectively prepared by aza-Claisen rearrangement of N-allyl-enammonium ions or C-alkylation of enamines. This allows rapid and convenient access to densely functionalized chiral building blocks.

Ultrasound-promoted synthesis of novel dispirocyclic frameworks from aza-Claisen rearrangements of Baylis–Hillman amines

A novel tetracyclic frameworks of dispiropyrrolizidines can be obtained in moderate to good yields via the 1,3-dipolar cycloaddition of azomethine ylides with dipolarophiles derived from aza-Claisen rearrangement of Baylis–Hillman amines. The transformations are highly regioselective and stereoselective, affording the desired compounds in reduced time and increased yields under ultrasound irradiation at room temperature. All the products are confirmed by 1H, 13C NMR, IR and MS spectra, while their molecular structures are elucidated by X-ray crystallography of a selected sample.

Ferrocenylimidazoline palladacycles as efficient catalysts for the aza‐Claisen rearrangement reaction of allylic imidates

AbstractChloride‐bridged palladacycle dimers 1 have been evaluated as catalysts for the aza‐Claisen rearrangement of allylic imidates 2 to the corresponding allyl amides 3. Cyclopalladated complexes 1b–e bearing electron‐donating substituents on imidazoline ring were identified as being superior catalysts because excellent yields were obtained without using silver salts for activation. In addition, a correlation between substituents on the imidazoline ring and catalytic activity of palladacycles was established. The electron‐deficient ligands and good solubility of catalysts in the reaction solution increase the catalytic activity. Copyright © 2008 John Wiley & Sons, Ltd.

Synthesis of Allylic Amines via Aza-Claisen Rearrangement

Branched chiral allylic amines are useful building blocks and the aza-Claisen rearrangement (aCR) allows their synthesis from readily available allylic alcohols. The C,N-ligand (FIP-Cl) developed by Peters and coworkers makes the catalyst exceptionally active. Thus, loadings as low as 0.05 mol% in Pd can be used. Although many enantioselective reactions have been reported, they usually require ˜10 mol% Pd loadings. Importantly, the reaction can generate N-substituted quaternary centers with excellent ee (i.e. 5f: 98% ee).

Studies on the aza-Claisen rearrangement of 4,5-dihydroxylated allylic trichloroacetimidates: the stereoselective synthesis of (2 R,3 S)- and (2 S,3 S)-2-amino-3,4-dihydroxybutyric acids

Two new synthetic approaches, involving substrate directed aza-Claisen rearrangements and aza-Claisen rearrangements mediated by chiral Pd(II) catalysts, have been developed for the stereoselective synthesis of (2 R,3 S)-2-amino-3,4-dihydroxybutyric acid, a dihydroxylated α-amino acid from the edible mushroom, Lyophyllum ulmarium and its (2 S,3 S)-unnatural diastereomer.

Catalytic Asymmetric Formation of Secondary Allylic Amines by Aza-Claisen Rearrangement of Trifluoroacetimidates

A catalytic asymmetric synthesis of unprotected secondary allylic amines based on the aza-Claisen rearrangement of N-aryl- and N-alkyl-substituted trifluoroacetimidates has been developed, which provides the targeted products with excellent enantioselectivity.

Silylcupration and Copper-Catalyzed Carbomagnesiation of Ynamides: Application to Aza-Claisen Rearrangement

Abstract Treatment of ynamides with silylcopper reagents resulted in silylcupration to afford (E)-β-silylenamides, after protonolysis, in good yields with high regio- and stereoselectivity. Reaction of ynamides having an allyl group on the nitrogen with Grignard reagents in the presence of a copper catalyst resulted in carbomagnesiation across the alkynyl unit and subsequent heating provided 4-pentenenitriles via aza-Claisen rearrangement.

Synthesis of Nearly Enantiopure Allylic Amines by Aza‐Claisen Rearrangement of Z‐Configured Allylic Trifluoroacetimidates Catalyzed by Highly Active Ferrocenylbispalladacycles

The development of the first highly active enantioselective catalyst for the aza-Claisen rearrangement of Z-configured allylic trifluoroacetimidates generating valuable almost enantiopure protected allylic amines is described. Usually Z-configured allylic imidates react significantly slower than their E-configured counterparts, but in the present study the opposite effect was observed. Z-Configured olefins have the principal practical advantage that a geometrically pure C=C double bond can be readily obtained, for example, by semihydrogenations of alkynes. Our catalyst, a C(2)-symmetric planar chiral bispalladacycle complex, is rapidly prepared from ferrocene in four simple steps. Key step of this protocol is an unprecedented highly diastereoselective biscyclopalladation providing dimeric macrocyclic complexes of fascinating structure. In the present study as little as 0.1 mol % of catalyst precursor were sufficient for most of the alkyl substituted substrates to give in general almost quantitative yields. NMR investigations revealed a monomeric structure for the active catalyst species. The bispalladacycle can also be used for the formation of almost enantiomerically pure allylic amines (ee > or =96 %) substituted with important functional groups such as ester, ketone, ether, silyl ether, acetal or protected amino moieties providing high-added-value allylic amine building blocks in excellent yield (> or =94 %). The preparative advantages should render this methodology highly appealing as a practical and valuable tool for the formation of allylic amines in target oriented synthesis.

Chiral Palladium Bis(acyclic diaminocarbene) Complexes as Enantioselective Catalysts for the Aza-Claisen Rearrangement

Palladium complexes of chiral bis(acyclic diaminocarbene) ligands with seven-membered chelate rings catalyze the aza-Claisen rearrangement of an allylic benzimidate to an allylic amide with moderate yields and enantioselectivities of 30–59% ee. The promotion of electrophilic catalysis by complexes of these ligands highlights their distinct stereoelectronic properties relative to those of common bis(N-heterocyclic carbenes).

Formation of Substituted Pyrroles via an Imine Condensation/Aza-Claisen Rearrangement/Imine−Allene Cyclization Process by MAOS

A diverse collection of pyrroles has been prepared using a one-pot, domino aldehyde/amine condensation, [3,3]-aza-Claisen rearrangement, imine-allene cyclization strategy. This protocol was accelerated by microwave irradiation and provided very good levels of conversion after reacting for only 30 min.

Quaternary Allylic Amines by Asymmetric Aza-Claisen Rearrangements

Quaternary Allylic Amines by Asymmetric Aza-Claisen Rearrangements

A Tandem Aza-Claisen Rearrangement and Ring Closing Metathesis Reaction for the Synthesis of Cyclic Allylic Trichloroacetamides

A one-pot tandem palladium(II)-catalyzed aza-Claisen rearrangement and ring closing metathesis process has been developed for the efficient synthesis of cyclic allylic trichloroacetamides. The use of chiral Pd(II) catalysts such as (S)-COP-Cl during the rearrangement stage results in the preparation of these compounds in excellent yields and in high enantiomeric excess.

Asymmetric Formation of Allylic Amines with N‐Substituted Quaternary Stereocenters by PdII‐Catalyzed Aza‐Claisen Rearrangements

With the ferrocene imidazoline palladacycle FIP-Cl as precatalyst, quaternary N-substituted stereocenters can be generated in an asymmetric aza-Claisen rearrangement. Excellent enantioselectivities are obtained even if R and R′ have a similar or identical size (see scheme: e.g. 96 % ee for CH3/CD3).

Microwave accelerated aza-Claisen rearrangements

The microwave-assisted thermal aza-Claisen rearrangement of allylic imidates and thiocyanates to the corresponding amides and isothiocyanates is investigated. Significant accelerations of the rearrangement of allylic imidates to amides and of allylic thiocyanates to isothiocyanates in comparison with standard thermal reactions is observed.

Practical Synthesis of 7-Prenylindole

7-Prenylindole is a useful building block for natural product and natural product analogue synthesis. While there have been several past syntheses of 7-prenylindole, none of them is very practical for its preparation on scale. Using an aza-Claisen rearrangement as the key step, 7-prenylindole has been prepared in four steps from indoline in 62% overall yield.